Studies will be made on the effects of planned variations in the structures of substrates, inhibitors, and enzymes on the kinetics and sterospecificity of enzymic reactions. Information will be sought about the structural features that contribute to productive fit, and the properties of precise fit that lead to high reactivity. Glycolamide esters will be studied in hydrolysis by alpha- chymotrypsin, to establish the effect of hydrogenbonding interaction in the c-terminal direction, as the alpha and beta- substituents are varied. Study will be made of hydrolysis by trypsin of glycolamide esters which lack a positive beta- substituent. Effects of neighboring hydrogen bonding interactions in the C- terminal direction and in the N- terminal direction will be examined in hydrolysis by an aminopeptidase and a carboxypeptidase respectively. Novel cyclized substrates, 2,4- diketomorpholines and pyroglutamates, will be examined for information as to the relative orientation of the alpha- acylamido and hydrolyzing peptide groups, and as to the reacting conformation of alpha- acylamido- groups. Competitive effects of binding and desolvation will be explored in study of inhibitors of varied structure, and compared with activation by the corresponding groups in substrates. Effects of the lifetime of enzyme- substrate complexes will be studied. Reactivity, and sterospecificity of native alpha- chymotrypsin and of enzyme modified at Met- l92 will be compared in hydrolysis of cyclized substrates and of beta- phenylpropionates containing varied alpha- substituents.